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Evaluation of brivaracetam, a novel SV2A ligand, in the photosensitivity model

From the University of Rome (D.G.A.K.-N.T.), Italy; Hôpital de la Timone (P.G.), Marseille, France; Hôpital CHU Charles Nicolle (D.P.), Rouen, France; Hôpital CHU de Bicêtre (P.M.), Kremlin Bicêtre, France; Epilepsiezentrum Kork (B.J.S.), Kehl-Kork, Germany; UCB Pharma SA (T.J., E.P., A.S.), Clinical Pharmacology, Braine-l'Alleud, Belgium; and CHRU Hôpital Civil (E.H.), Strasbourg, France.

Address correspondence and reprint requests to Dr. Dorothée Kasteleijn-Nolst Trenité, University of Rome "La Sapienza" II, Via Vitorchiano 81, I-00189 Rome, Italy Dorothee.Kasteleijn{at}uniroma1.it, dkasteleijn{at}planet.nl

Objective: To assess the activity of brivaracetam, a novel SV2A ligand, in the photosensitivity model as a proof-of-principle of efficacy in patients with epilepsy.

Methods: A subject-blind placebo-controlled study in patients with photosensitive epilepsy was performed to investigate the effect of single-dose brivaracetam (10, 20, 40, or 80 mg) on photosensitive responses. Each patient was exposed to intermittent photic stimulation that evoked a generalized photoparoxysmal EEG response. Individual standard photosensitivity ranges (SPRs) were recorded post-placebo (day –1) and post-brivaracetam until return to baseline (day 1 to 3). Plasma concentrations of brivaracetam and any concomitant antiepileptic drugs were determined.

Results: Of the 18 evaluable patients, none achieved SPR abolishment post-placebo, whereas 14 (78%) achieved complete abolishment post-brivaracetam. Decrease in SPR was seen in 8 patients (44%) post-placebo compared to 17 (94%) post-brivaracetam. Duration of response was twice as long post-brivaracetam 80 mg (59.5 hours) compared with lower doses, although the overall effect was not dose-dependent. Time to maximal photosensitive response was dose-related with the shortest time interval observed at the highest dose (0.5 hours post-brivaracetam 80 mg). The area under the effect curve (SPR change from pre-dose vs time) appeared linearly correlated with the area under the plasma concentration curve. Brivaracetam was well tolerated. The most common adverse events were dizziness and somnolence.

Conclusions: Our findings show that brivaracetam clearly suppresses generalized photoparoxysmal EEG response. As such, investigations of the antiepileptic properties and tolerability of brivaracetam are warranted in further clinical studies of patients with epilepsy.

Supplemental data at www.neurology.org

This study was sponsored by UCB Pharma SA, Belgium. D.G.A Kasteleijn-Nolst Trenité is supported by a EU FP6 grant, Marie Curie Excellence Chair 024224: Visual Sensitivity.

Disclosure: T. Jacobs, E. Pigeolet, and A. Stockis are employees of UCB Pharma SA, Belgium. D.G.A. Kasteleijn-Nolst Trenite, P. Genton, D. Parain, P. Masnou, and E. Hirsch have participated in pharmacologic studies sponsored by various companies to develop new antiepileptic drugs.

Received December 12, 2006. Accepted in final form April 5, 2007.

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